Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography

Yu, Qingzhen1,2,3,4; Kumata, Katsushi5; Rong, Jian1,2; Chen, Zhen1,2; Yamasaki, Tomoteru5; Chen, Jiahui1,2; Xiao, Zhiwei1,2; Ishii, Hideki5; Hiraishi, Atsuto5; Shao, Tuo1,2; Zhang, Yiding5; Hu, Kuan5; Xie, Lin5; Fujinaga, Masayuki5; Zhao, Chunyu1,2; Mori, Wakana5; Collier, Thomas1,2; Haider, Ahmed1,2; Tomita, Susumu6; Zhang, Ming-Rong5; Liang, Steven1,2

2022-06-01

10.1021/acs.jmedchem.2c00377

JOURNAL OF MEDICINAL CHEMISTRY   Impact Factor & Quartile

0022-2623

1520-4804

The transmembrane alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA) receptor regulatory protein gamma-8 (TARP gamma-8) constitutes an auxiliary subunit of AMPA receptors, which mediates various brain functions including learning and memory. TARP gamma-8 has emerged as a promising therapeutic target for central nervous system disorders. Despite considerable efforts, previously reported TARP gamma-8 PET radioligands, such as [C-11]TARP-1903 and [C-11]TARP-1811 series, were plagued by limited brain uptake and/or high nonspecific binding in vivo. Herein, we developed two novel C-11-labeled probes, [C-11]8 and [C-11]15 (also named as [C-11]TARP-2105), of which the latter exhibited a reasonable brain uptake as well as specific binding toward TARP gamma-8 both in vitro and in vivo, as confirmed by blocking experiments with the commercially available TARP gamma-8 inhibitor, JNJ-55511118 in the TARP gamma-8-rich hippocampus. Overall, [C-11]15 exhibited promising tracer characteristics and proved to be a lead positron-emission tomography ligand for the non-invasive quantification of TARP gamma-8 in the mammalian brain.

SCI

English

Others

NIH["MH120197","AG073428","AG074218","MH078939"] ; JSPS KAKENHI[20H03635] ; AMED Moonshot Research and Development Program[21zf0127003h001]

Pharmacology & Pharmacy

Chemistry, Medicinal

WOS:000823308300001

AMER CHEMICAL SOC

CHEMISTRY

Web of Science

1.Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA
2.Harvard Med Sch, Boston, MA 02114 USA
3.Southern Univ Sci & Technol Hosp, Med Res Ctr, Shenzhen 518055, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Guangdong, Peoples R China
5.Natl Inst Quantum Sci & Technol, Inst Quantum Med Sci, Dept Adv Nucl Med Sci, Chiba 2638555, Japan
6.Yale Univ, Dept Cellular & Mol Physiol, Dept Neurosci, Sch Med, New Haven, CT 06510 USA

Yu, Qingzhen,Kumata, Katsushi,Rong, Jian,et al. Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography[J]. JOURNAL OF MEDICINAL CHEMISTRY,2022.

Yu, Qingzhen.,Kumata, Katsushi.,Rong, Jian.,Chen, Zhen.,Yamasaki, Tomoteru.,...&Liang, Steven.(2022).Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography.JOURNAL OF MEDICINAL CHEMISTRY.

Yu, Qingzhen,et al."Imaging of Transmembrane AMPA Receptor Regulatory Proteins by Positron Emission Tomography".JOURNAL OF MEDICINAL CHEMISTRY (2022).